This invention relates to methods and devices for treatment of diseases that include congestive heart failure, chronic renal failure and hypertension. Specifically, the invention relates to improving conditions in patients by blocking or at least modifying (modulating) signals via the renal nerve.
Heart Failure
Congestive Heart Failure (CHF) is a form of heart disease that is becoming ever more common. The number of patients with CHF is expected to grow in increasing numbers as the so-called “Baby Boomers” reach 50 years of age. CHF is a health condition that occurs when the heart becomes damaged, resulting in a reduced blood flow to the organs of the body. If blood flow decreases sufficiently, kidney function becomes impaired and results in fluid retention, abnormal hormone secretions and increased constriction of blood vessels. These results increase the stress on the heart to do work, and further decrease the capacity of the heart to pump blood through the kidney and vascular circulation system. This reduced capacity further reduces blood flow to the kidney. It is believed that this cycle of reduced kidney perfusion is the principal non-cardiac cause perpetuating a patient's downward spiral into CHF. Moreover, the fluid overload and associated clinical symptoms resulting from these changes are predominant causes for excessive hospital admissions, reduced quality of life and overwhelming costs to the health care system.
While many different diseases may cause initial damage to the heart, once such damage is present, CHF is identifiable under two types: Chronic CHF and Acute CHF. Despite its name, the chronic form is the less acute form of the two but is a longer term, slowly progressive, degenerative disease, and may lead to cardiac insufficiency. Chronic CHF is clinically categorized by the patient's mere inability to exercise or perform normal activities of daily living.
By contrast, patients with Acute CHF may experience a more severe deterioration in heart function than those with Chronic CHF. The Acute form results in the inability of the heart to maintain sufficient blood flow and pressure to keep vital organs of the body alive. This condition can occur when extra stress (such as by infection) significantly increases the workload on the heart in a patient with an otherwise stable form of CHF. By contrast to a mere stepwise downward progression that is observable in patients with Chronic CHF, a patient suffering Acute CHF may deteriorate rapidly from even the earliest stages of CHF to severe hemodynamic collapse. Moreover, Acute CHF can occur within hours or days following an Acute Myocardial Infarction (AMI), which is a sudden, irreversible injury to the heart muscle, identified in common parlance as a heart attack.
Kidney Failure
Against this background, the kidneys are known to play an important regulatory role in maintaining the homeostatic balance of the body. The kidneys eliminate foreign chemicals from the body, regulate inorganic substances, and function as endocrine glands to secrete hormonal substances like renin and erythropoietin. The main functions of the kidney are to maintain the water balance of the body and control metabolic homeostasis by making the urine more or less concentrated, thus either reabsorbing or excreting more fluid. However, when renal disease arises, some otherwise ordinary and regular physiological functions may become detrimental to the patient's health. When this occurs, the process is known as overcompensation. In the case of Chronic Renal Failure (CRF) the event of overcompensation may manifest itself as hypertension that has the effect of damaging the heart and blood vessels, and can eventually result in a stroke or death. Thus, without proper function by the kidneys, a patient may suffer water retention, reduced urine flow and an accumulation of waste toxins in the blood and body. These conditions resulting from reduced renal function, or renal failure (kidney failure), tend to increase the workload placed upon the heart. In a patient, simultaneous occurrence of both CRF and CHF may cause the heart to further deteriorate as the water build-up and blood toxins accumulate due to the poorly functioning kidneys and may, in turn, cause the heart further harm.
Nervous System
It has been observed, in connection with human kidney transplantation, that there is evidence to suggest that the nervous system plays a major role in kidney function. It was noted for example that after a transplant, when all the renal nerves are severed, the kidney was observed to increase excretion of water and sodium. This phenomenon has also been observed in animals when renal nerves are cut or chemically destroyed. The phenomenon has been termed “denervation diuresis” because the denervation acted on a kidney in a similar way to a diuretic medication. Later, observation of “denervation diuresis” was found to be associated with the vasodilatation of the renal arterial system that led to the increase of the blood flow through the kidney. This observation was confirmed by the observation in animals that reducing blood pressure supplying the kidney could reverse the “denervation diuresis”.
It was also observed that after several months passed after the transplant surgery in successful cases, the “denervation diuresis” in transplant recipients stopped, and the kidney function returned to normal. Initially, it was believed that “renal diuresis” is merely a passing phenomenon and that the nerves conducting signals from the central nervous system to the kidney are not essential for kidney function. Later discoveries led to the present generally held conclusion that the renal nerves have an ability to regenerate, and that the reversal of the “denervation diuresis” is attributable to the growth of the new nerve fibers supplying kidneys with the necessary stimuli.
In summary then, it is known from clinical experience and also from the large body of animal research that stimulation of the renal nerve leads to the vasoconstriction of blood vessels supplying the kidney, decreased renal blood flow, decreased removal of water and sodium from the body and increased renin secretion. It is also known that reduction of the sympathetic renal nerve activity, achieved by denervation, can reverse these processes.
Steps Taken in the Prior Art, and Problems Arising
There has therefore already been identified a need in the art for methods and devices that may apply the observed effects set forth above to halt and reverse the symptoms of Congestive Heart Failure. Thus, certain methods and devices have already been commercialized in the art to reduce renal nerve activity, in order to meet the aforesaid need. For example, the following patents are directed to the stated need: U.S. Pat. Nos. 7,620,451, 6,978,174, and 8,145,316, all of which are incorporated herein by reference. In some approaches configured to induce selective damage to the renal nerves (renal denervation), manufacturers have developed and used radio frequency (RF) catheters, or drug delivery devices, which, while being minimally invasive, have tradeoffs in terms of ease of use, treatment accuracy, and regulatory complexity. An additional problem is that some patients may require a follow-up treatment with these treatments in cases where nerves are not adequately disrupted after receiving initial denervation therapy, and this introduces the complexity of having to apply multiple treatments over a period of time for the same condition.
Thus there is today an additional need to overcome the limitations and challenges of contemporary RF-based renal denervation therapy. RF contact requires energy transmission through contact with the targeted tissue. The manner of contact affects the intensity of RF energy transmission, wherein a smaller contact surface is desired to produce intensified tissue and nerve ablation. Once RF ablation has begun, tissue in the vicinity of a contact surface becomes desiccated as water molecules are induced into a vibrational state to the point of generating substantial heat within the tissue. An injury response is subsequently induced, and this has been shown to disrupt neural pathways passing through the zone of injury. However, some problems with contemporary RF methods for renal denervation are included in the list set forth here: (1) Renal artery bending motion may make accurate catheter-to-vessel contact difficult to reliably control, and therefore may make it difficult to control the degree and location of the desired RF-based injury; (2) Many point-based RF catheters only denervate a single contact point at a time, and cannot reliably guarantee the disruption of nerves around the entire renal artery circumference; (3) To accommodate problem no. 2, single point-based RF therapy has been developed, but this generally requires multiple ablations with targeted positions around the circumference of the renal artery; this is thought to increase the likelihood of disrupting the bundle of nerves passing by the renal artery; (4) If RF induced injury is too intensely localized within a short span of artery, there is a possibility of arterial occlusion or thrombosis.
In order to manage the above challenges, drug-driven therapies have been introduced to locally deliver chemical agents to induce injury to the renal nerves in the peri-adventitial space. However, these “combination device” therapies are costly and require extensive regulatory cost to facilitate approval.
Need in the Art
Thus, there is a need in the medical arts to produce a therapy which is relatively simple, accurate, effective, and/or requires less costly existing equipment and methods. The present invention addresses these and other needs.